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The Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 9 4177-4185
Copyright © 2002 by The Endocrine Society

Original Article

Abnormal Bone Mineral Accrual in Adolescent Girls with Anorexia Nervosa

Leslie A. Soyka, Madhusmita Misra, Aparna Frenchman, Karen K. Miller, Steven Grinspoon, David A. Schoenfeld and Anne Klibanski

Neuroendocrine Unit and General Clinical Research Center (M.M., A.F., K.K.M., S.G., D.A.S., A.K.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; and Department of Pediatrics (L.A.S.), University of Massachusetts Medical School, Worcester, Massachusetts 01655

Address all correspondence and requests for reprints to: Anne Klibanski M.D., Neuroendocrine Unit, Bulfinch 457, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: . aklibanski{at}partners.org

Abstract

Anorexia nervosa (AN) is increasingly common in adolescent girls and occurs at a time of peak bone mass formation. Osteopenia is common in adolescent girls with AN, and in a cross-sectional study, we have reported low bone formation markers in such girls. To determine the impact of chronic undernutrition on bone mineral accrual in contrast to healthy controls, we prospectively measured bone mineral density (BMD) and body composition by dual energy x-ray absorptiometry, bone metabolism markers, and nutritional and hormonal status at baseline, 6 months, and 12 months in 19 adolescent girls with AN (mean ± SEM, 15.4 ± 0.4 yr) and 19 controls of comparable chronological and skeletal age. Overall, nutritional status in subjects with AN improved (mean percentage increase in body mass index from baseline, 9.2 ± 1.9% and 15.2 ± 2.6% at 6 and 12 months, respectively), with 11 subjects having recovered weight at 12 months. However, lumbar BMD at 12 months (AN, 0.88 ± 0.02 g/cm2, vs. control, 0.98 ± 0.03 g/cm2; P = 0.008) remained significantly reduced in AN compared with controls, even in recovered subjects. This was due to significant increases in lumbar BMD in controls vs. no change in AN subjects over the year (0.003 ± 0.001 g/cm2·month vs. 0.000 ± 0.001 g/cm2·month, respectively; P = 0.04). The most significant determinant of change in lumbar BMD at 12 months was change in lean body mass in both AN (r = 0.62; P = 0.008) and control (r = 0.80; P = 0.0006) groups. There were significant increases in surrogate markers of bone turnover in subjects with AN compared with controls as assessed by osteocalcin (AN, 0.9 ± 0.4 µg/liter·month, vs. control, -1.1 ± 0.4 µg/liter·month; P = 0.0007), bone-specific alkaline phosphatase (AN, 0.6 ± 0.5 U/liter·month, vs. control, -1.5 ± 0.4 U/liter·month; P = 0.002), deoxypyridinoline [AN, 0.1 ± 0.1 nmol/mmol creatinine (cr) ·month, vs. control, -0.4 ± 0.1 nmol/mmol cr·month; P = 0.005], and N-telopeptide (AN, 4 ± 4 nmol BCE/mmol cr/month, vs. control, -9 ± 4 nmol BCE/mmol cr/month; P = 0.01). Changes in IGF-I levels over the year were highly correlated with changes in bone turnover over the same period in AN (osteocalcin, r = 0.77; P = 0.001; deoxypyridinoline, r = 0.66; P = 0.01). A rise in N-telopeptide over the year was correlated with an increase in all bone mineral measures, including lumbar bone mineral content (r = 0.58; P = 0.03) and BMD (r = 0.53; P = 0.05) and total bone mineral content (r = 0.69; P = 0.006) and BMD (r = 0.69; P = 0.006) in the AN group.

Therefore, despite recovery over 1 yr, poor bone mineral accrual persists in adolescent girls with AN in contrast to rapid bone accrual in healthy girls. Normalization of bone turnover markers occurs in association with nutritional recovery and an increase in the nutritionally dependent bone trophic factor IGF-I. A rise in bone turnover markers may be an early indicator of increase in BMD in recovering girls with AN.




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